Eradication of HIV from CNS/Myeloid Reservoirs Program
This program supports innovative research in five areas: (1) basic research to identify and characterize persistent/latent HIV-1 in cells derived from the central nervous system (CNS), such as macrophages, microglia, T-cells, and astrocytes, in the setting of suppressive antiretroviral therapy (ART); (2) basic research to determine the mechanisms involved in the temporal establishment, maintenance, and resurgence of persistent/latent HIV-1 in the CNS, in relationship to the timing of antiretroviral therapy; (3) development of physiologically relevant animal models and CNS-based cellular assays that recapitulate HIV-1 persistence and latency in the presence of effective ART; (4) feasibility assessments of current and emerging eradication approaches to have successfully reactivated persistent HIV-1 from CNS-derived cells such as macrophages, microglia, T-cells, and astrocytes; and (5) assessment of CNS toxicity and adverse impact of current and emerging eradication strategies.
Areas of Emphasis
- Identify all potential latent and persistent HIV-1 CNS cellular reservoirs and discover the molecular mechanisms involved in establishment, maintenance, and resurgence of CNS-based HIV-1 reservoirs in relationship to the effects and timing of ART.
- Elucidate CNS immune escape mechanisms of persistently/latently infected cells in the context of ART and understand the role of inflammation in maintaining HIV-1 persistence in CNS.
- Develop physiologically relevant cell-based assays and adapt existing animal models to recapitulate HIV-1 persistence/latency in the presence of effective ART, and adapt the same for testing viral eradication strategies.
- Discover novel neuroimaging approaches and cellular biomarkers to detect latently and persistently infected cells in the CNS.
- Develop innovative eradication strategies with increased blood-brain barrier permeability and CNS targeting to eliminate latent/persistent CNS reservoirs, and identify novel silencing approaches to prevent viral resurgence in the CNS upon cessation of ART.
- Assess the impact of the current HIV-1 eradication strategies on the CNS relating to neuroinflammation and neurocognitive outcomes.
Jeymohan Joseph, Ph.D.
5601 Fishers Lane, Room 9G20
Rockville, MD 20852